The Impact of Stress on Immune Systems and Its Relevance to Mental Illness

Stress due to adverse and demanding conditions alters immune functions. How innate and adaptive immune systems respond to stress and affect neural processes remains unclear. Rodent studies have demonstrated crucial roles of stress-induced immune responses for depressive- and anxiety-like behaviors. In the periphery, stress evokes the mobilization of neutrophils and monocytes to the circulation via sympathetic nerves and glucocorticoids. These myeloid cells are thought to promote depressive- and anxiety-like behaviors by infiltrating the brain's perivascular space, releasing cytokines, and affecting vascular endothelial functions. In the brain, stress activates microglia via innate immune receptors TLR2/4. The activated microglia in the medial prefrontal cortex secrete cytokines and alter neuronal morphology and activity in their vicinity. In subcortical brain areas, prostaglandin (PG) E released from the activated microglia attenuates the dopaminergic projection to the medial prefrontal cortex via PGE receptor EP1. These multiple actions of microglia promote depressive-like behavior in concert. These rodent findings may be translatable to depression that clinical studies have associated with brain and peripheral inflammations. Understanding causal relationships between immune and neural alterations under stress might be exploitable to develop inflammation-targeting therapeutics for mental illness.